Aging in female rodents is associated with a gradual decline in litter size which culminates in infertility. In the C57BL/6 mouse such changes are evident at eight months of age and gradually increase until, by 15-16 months of age, most females are sterile. The proposed research will examine with light and electron microscopy the histological changes which occur in the ovaries and pituitaries of aged C57BL/6 mice (12-15 months of age) when compared with those of younger mature females (3-5 months of age) during four stages of pregnancy (1, 4, 9 and 16 days). Any age-related morphological changes will then be associated with circulating plasma levels of progesterone, estrogen, prolactin, lutenizing hormone (LH) and follicle-stimulating hormone (FSH) as determined by radioimmunoassay (RIA). Ovaries and pituitaries from another group of C57BL/6 mice, 16-20 months of age, will be examined and plasma and pituitary levels of LH, FSH and prolactin levels (measured by RIA) compared with those of younger mature females. The correlation between cytological changes in the ovary and pituitary with regard to circulating levels of reproductive hormones during aging should provide data on the causes of reproductive dysfunction and eventual sterility. A primary objective of the proposed research is to determine if the C57BL/6 mouse might serve as an effective animal model for experiments leading to a better understanding of age-related changes preceding and/or inducing menopause in the human.